Inflammation in the bone marrow stem cell niche. A driver of bone marrow failure and leukemia?
Patients with bone marrow failure (such as those suffering from the Shwachman-Diamond-Syndrome) have an increased risk of developing acute myeloid leukemia. Possibly genetic changes in blood stem cells have a crucial role in this: genetic alterations render the cells less prone to stress caused by inflammation, but those stress insensitive cells are more prone to develop into malignant cells.
This research investigates how and why genetic alterations happen in the Shwachman-Diamond-Syndrome, how selection for these alterations occurs, leading to cells that are insensitive to stress caused by inflammation and whether this leads to increased risk of leukemia (AML).
Obtaining insight in the biological functioning, how cells become inflammatory stress resistant and whether this resistance contributes to an elevated risk to develop a malignancy is the first step to identify and develop new therapeutic possibilities.
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Role Erasmus MC: